N-nitroso compounds comprise one of the most versatile and potent classes of carcinogens. As they are present in or formed from many environmental sources they are suspected as contributing to the etiology of human cancer. Results of previous studies including those described in the "Progress Report" have indicated that the initial chemical event leading to mutation and perhaps tumor induction by N-nitroso compounds is the interaction of nitroso derived alkyl diazonium ion or carbonium ion with DNA bases. The alkylating efficiencies of and product distributions produced by N-nitroso compounds may vary between N-nitroso compounds and thus affect their mutagenic potencies. In addition cellular responses to alkylation may enhance or attenuate the effects of alkylation. These responses are not so well understood and are dose-dependent. This grant proposal addresses itself to the problems of relative alkylation and mutation inducing efficiencies of N-nitroso compounds and the biological responses to alkylation by N-nitroso compounds at different dose levels. The main areas of investigation in the project are: 1. Measurement of mutagenic potencies and rates of decomposition of N-nitroso compounds. These measurements will allow the expression of mutagenic potencies in terms of mutants per nmole of mutagen metabolized, and will be carried out at many dose levels using Salmonella tester strains. 2. Investigations into the effects of bacterial strain, growth rate and growth phase on mutagenesis induced by N-nitroso compounds. These factors may influence contributions to mutagenesis attributable to differing DNA repair systems or different extents of DNA repair. 3. Investigations into the effectiveness of subthreshold doses of N-nitroso compounds in enhancing mutagenesis induced by other N-nitroso compounds and other classes of mutagens (comutagenesis). 4. Investigations into the relationship between O6-alkylation of bacterial DNA by N-nitroso compounds and mutagenesis induced by N-nitroso compounds. Effects of dose-levels, bacterial strains and bacterial growth rates will also be investigated. 5. Effects of inhibitors of error-prone DNA repair on mutagenesis induced by N-nitroso compounds, in several bacterial strains.